Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.
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PMID:Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989). 174 13

Primidone, phenytoin, or phenytoin and primidone in combination were given to healthy Beagle dogs for 6 months. Serum biochemical changes in dogs given primidone alone or phenytoin and primidone in combination for the entire 6-month test period included increased activities of alanine aminotransferase, alkaline phosphatase (AP), and gamma-glutamyltransferase, and decreased concentrations of albumin and cholesterol. Changes in dogs given phenytoin alone were limited to increased AP activity and decreased albumin concentration. Sulfobromophthalein excretion and conjugated bile acid concentration were within normal limits. All dogs given primidone alone or phenytoin alone remained clinically healthy throughout the treatment period. Three of 8 dogs given both drugs in combination became clinically ill after 9, 14, and 15 weeks of treatment, and were euthanatized. Two of the dogs developed clinical jaundice. In addition to the serum biochemical abnormalities observed in clinically healthy dogs, these dogs developed hyperbilirubinemia, delayed sulfobromophthalein excretion, and increased conjugated bile acid concentrations. Histologic examination of the liver showed intracanalicular casts of bile pigment typical of intrahepatic cholestasis in all 3 dogs. Histologic findings characteristic of treated dogs included hepatocellular hypertrophy attributable to hyperplasia of the smooth endoplasmic reticulum. Single-cell necrosis and multifocal lipidosis were observed in individuals of all treatment groups. Electron microscopy of the liver showed dilated bile canaliculi and damaged sinusoidal epithelium in dogs given both drugs. The elevated serum AP activity, associated with anticonvulsant drug therapy, was found to be exclusively the liver isoenzyme by cellulose acetate electrophoresis. The hepatic AP was localized to primarily the canalicular membranes by enzyme histochemistry. There was a statistically significant positive correlation between the AP activities of liver and serum. The results of this study indicate that long-term administration of anticonvulsant drugs to dogs is associated with clinical, serum biochemical, and histologic evidence of hepatic dysfunction. High drug dosage contributed most to abnormal serum biochemical test results, and combining phenytoin with primidone was responsible for more severe electron microscopic lesions of the liver of surviving dogs and for the death of 3 dogs.
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PMID:Effects of long-term primidone and phenytoin administration on canine hepatic function and morphology. 285 43

Time- and dose-dependent correlations of monochlorobenzene (CB) hepatotoxic effects were studied in view of (1) assumed mechanistic similarities to bromobenzene (BB), (2) the paucity of these data for CB, and (3) the relatively greater environmental importance of CB compared with BB. An ip dosage of 9.8 mmol/kg CB (approximately equal to LD10) produced evidence of liver toxicity over a 72-hr time course. Sulfobromophthalein (BSP) retention was maximized 3-16 hr post-treatment and normalized after 72 hr, whereas plasma alanine aminotransferase activity (ALT) and morphological evidence of damage were maximized about 48 hr after dosing. Maximal covalent binding to liver protein (3.07 nmol/mg) had occurred by 24 hr and approximately 36% of the administered dose had appeared in the urine by 48 hr. Liver and plasma CB concentrations were proportionally increased over the dosage range 2.0-14.7 mmol/kg but marked centrolobular necrosis and ALT elevations were seen only at the two highest dosages (9.8 and 14.7 mmol/kg). On the other hand, all doses depressed hepatic glutathione (GSH) to between 30 and 40% of control by 4 hr. Evidence of rapid recovery was evident at 2.0 and 4.9 mmol/kg but GSH levels remained low through 8 hr after 9.8 or 14.7 mmol/kg. Liver/body weight ratios were increased to a similar extent at all dosages when measured 24 hr post-treatment. Urinary excretion ranged from 59% at the low dosage to only 19% at the highest dosage by 24 hr. Dose-related covalent binding to liver protein at 24 hr occurred up to 9.8 mmol/kg but the binding associated with 14.7 mmol/kg was equivalent to that seen with the 4.9 mmol/kg dosage (1.6 nmol/mg protein). Cytochrome P-450 levels were depressed to between 50 and 80% of control 24 hr post-treatment with no clear dose relationship. While the hepatotoxic effects of CB and BB appear similar, these data suggest that some mechanistic differences are involved.
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PMID:Temporal and dose-response features of monochlorobenzene hepatotoxicity in rats. 398 88

Advanced chronic hepatic disease was observed in 5 dogs that had received anticonvulsant drug therapy for 2 to 3 years. Clinical signs included anorexia, weakness, and restlessness, and 2 dogs also had ascites. There were remarkable increases in the serum activities of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase. The total serum bile acid concentration was high in 3 of 4 dogs that were tested. Sulfobromophthalein excretion was delayed in all dogs. Histologic examination of liver specimens from 4 of the dogs demonstrated macronodular or micronodular cirrhosis.
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PMID:Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs. 711 8

Cats with the Chediak-Higashi Syndrome (CHS) have partial oculocutaneous albinism, a bleeding tendency, and enlarged cytoplasmic granules in many cell types including those in the liver and kidney. Hepatic and renal function was evaluated in six CHS and six age-matched control cats to determine if the functions of these organs were compromised by the CHS trait. Serum concentrations of alanine aminotransferase, alkaline phosphatase, and total bilirubin were determined to assess the status of the liver. Sulfobromophthalein retention tests were also performed. Renal function was evaluated by determination of (14)C-inulin clearance; blood urea nitrogen and serum creatinine concentrations; 24-hour protein/creatinine ratios, percent clearance ratios of calcium, phosphorus, sodium, potassium and chloride; and urinalysis values. The CHS cats were not significantly (P > 0.05) different from the control cats in any of the above tests. Use of a non-parametric statistical test did reveal a mild difference (P = 0.047) in 24-hour protein excretion between CHS and control cats. Complete blood counts were performed, and the packed cell volume and hemoglobin concentrations were significantly lower (P< 0.05) in the CHS cats than in the control cats.
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PMID:Evaluation of hepatic and renal function in cats with chediak-higashi syndrome. 1522